Braincells, Inc. Announces the Successful Completion of a Multiple Ascending Dose Study of BCI-838, a Group II mGluR2/3 Antagonist, and the Company's Plans for a Proof-of-Concept Study in Patients with Treatment-Resistant Depression

SAN DIEGO, Nov. 5, 2012 /PRNewswire/ -- BrainCells, Inc. (BCI), a leading biotechnology company developing novel compounds for the treatment of central nervous system (CNS) diseases, announced the successful completion of their Phase 1 multiple ascending dose (MAD) study of BCI-838, the oral prodrug for the company's Group II mGluR2/3 antagonist, BCI-632. BCI will advance the clinical development program of the compound by initiating a Proof-of-Concept (PoC) study in patients with treatment-resistant depression (TRD) in early 2013.

The MAD study evaluated BCI-838 for safety, tolerability, pharmacokinetics and pharmacodynamic effect in healthy male and female subjects. Three different dose levels of BCI-838 were administered orally once daily for 7 days. The study's pharmacokinetic results indicate that all 3 doses of BCI-838 met or exceeded exposures of BCI-632 expected for the treatment of TRD. BCI-838 showed a favorable safety profile with no treatment-related trends in clinical laboratory results, vital sign measurements, 12 lead ECG results, or physical examination findings. In addition, the drug was well-tolerated within and up to the dose levels predicted for efficacy. Adverse events (AEs), which were mild to moderate in intensity, were transient, and resolved without sequelae. As a pharmacodynamic endpoint, quantitative electroencephalograms (qEEG) were included on day 1 and day 7 of the study. At all 3 dose levels, significant changes in several frequency bands were observed at both time points indicative of the drug's brain penetration and engagement of its target.

"BCI-632's biological activity triggers changes in the brain through a mechanism similar to that for ketamine, an intravenous drug which has shown remarkable efficacy in treating patients with TRD. Since ketamine is associated with a number of unwanted side effects such as short-term dissociation and psychosis, BCI-838 has the potential to significantly improve the way the disease is managed for these patients," said Robert Williamson, Chief Executive Officer.

BCI-632 increases synaptic glutamate by inhibiting the mGlu2/3 auto-receptor, which is located predominantly at the pre-synaptic site. As in the case of ketamine, the long-lasting efficacy of BCI-632 can be blocked by either inhibition of AMPA receptors, mTOR or the BDNF signaling pathway. In addition, BCI-632 also stimulates serotonin release and, after chronic dosing, hippocampal neurogenesis.

"BCI-838 is an oral prodrug for the active agent BCI-632 that is the leading mGluR2/3 antagonist in development," said John Hutchinson, Ph.D. Senior Vice President of Research. "The successful completion of this Phase 1 trial, coupled with the encouraging qEEG data, offers promise that the drug will demonstrate efficacy in further clinical studies."

"BCI-838 may yield meaningful clinical benefits for patients suffering from TRD. We believe that BCI-838 may generate early antidepressant responses similar to ketamine with a better safety profile and less adverse event liability. Unlike ketamine, BCI-838 is an oral drug with no need for intravenous administration. Furthermore, the neurogenic effect of BCI-838 in the hippocampus suggests that BCI-838 may be a novel treatment for a broader population of patients with mood or cognitive disorders," said Steven D. Targum. M.D., Chief Medical Officer. "We look forward to the clinical advancement of this compound in a PoC study targeted for initiation in patients with TRD at the beginning of 2013."

About TRD and MDD

Major Depressive Disorder (MDD) is a highly prevalent disorder causing marked social and economic problems for affected patients and their families. According to the World Health Organization, MDD is the leading cause of disability worldwide. MDD is associated with high morbidity contributing to greater health risks and a high risk for mortality.

Many depressed patients are not correctly diagnosed and may receive no treatment at all. Many other MDD patients who are treated do not achieve a full remission of their symptoms despite treatment. In the NIMH sponsored STAR*D study (Sequenced Treatment Alternatives to Relieve Depression), only 36.8% of patients achieved remission with citalopram, a first-line antidepressant treatment in the sequence. In fact, several other studies have also shown that less than 50% of treated MDD patients achieve more than a 50% reduction of their symptoms. Some MDD patients appear to be resistant to antidepressant treatment. Treatment resistant depression (TRD) is defined as the failure to fully respond to an antidepressant treatment despite having had an adequate dose and duration of treatment. Despite the availability of many new therapeutic agents in recent decades, these medications have revealed issues related to limited efficacy and tolerability. Currently available antidepressants are associated with adverse events, such as gastrointestinal symptoms, agitation, and sexual dysfunction that may affect treatment compliance.

About BrainCells Inc.

BrainCells Inc. is a clinical stage company that is developing novel therapies for the treatment of central nervous system (CNS) diseases based on the principal of blocking or antagonizing select metabotropic glutamate receptors (mGluR). Glutamate, an amino acid, functions as a neurotransmitter and glutamate receptors are implicated in a number of CNS diseases due to their central role in excitation of neural cells. BrainCells, in conjunction with its partner Taisho Pharmaceutical Co., Ltd., has pursued the development of a novel mGluR2/3 antagonist, BCI-632. The compound and its prodrug, BCI-838, have been extensively studied in preclinical models suggesting broad therapeutic potential in the treatment of MDD, TRD and potentially Alzheimer's disease (AD).

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